MODULATION OF NEUTROPHIL FUNCTIONS BY INFLAMMATORY MEDIATORS IN PERIODONTAL DISEASES It is hypothesized that neutrophils are primed by inflammatory mediators produced during periodontal disease to release toxic factors resulting in tissue destruction. Further, periodontal patients with hyperresponsive monocyte trait have neutrophil functions different normal monocyte response due to discrete profiles of PMN modulatory mediators produced by hyperresponsive monocytes. We propose to: 1) compare neutrophils functions (respiratory burst, and phagocytosis and killing of periodontal pathogens) among three different periodontal disease types and insulin dependent diabetes mellitus (IDDM) patients with periodontal disease; 2) correlate neutrophil functions of patients with different monocytic phenotypes determined by quantitating a panel of mediators expressed by peripheral blood monocytes in response to selected agonists, and 3) determine individual cytokine influence on neutrophil functions. Sixty-one subjects were recruited for the study, 11 were excluded from the data analy sis for technical reasons. The final sample included 21 adult periodontitis, 13 early onset periodontitis, 5 IDDM, 6 refractory periodontitis, and 15 controls. Respiratory burst, and phagocytosis and killing of P. gingivalis and A. actinomycetemcomitans were performed. Preliminary analysis revealed no difference among patients and controls in respiratory burst. Phagocytosis and killing assay slides are being analyzed. Assays of monocytes cytokines profiles (TNF-a, IL-1B, IL-6, IL-8 and PGE2) revealed dichotomies among the subjects that were independent of their clinical diagnosis. To date the data indicate significant correlations between IL-6, IL-8 and PGE2, that are significantly associated with exaggerated PMN respiratory burst. Sources of neutrophil killing mechanisms of P. gingivalis indicate an absolute requirement for respiratory burst and suggest a role for myeloperoxidase. The identification of the influences of cytokines and other inflammatory mediators on neutrophil function s will enhance our knowledge of the pathogenesis of periodontal disease.